Total Synthesis of Zwitterionic Tetrasaccharide Repeating Unit from Bacteroides fragilis ATCC 25285/NCTC 9343 Capsular Polysaccharide PS A1 with Alternating Charges on Adjacent Monosaccharides.

The tetrasaccharide repeating unit of zwitterionic polysaccharide A1 (PS A1) from Bacteroides fragilis ATCC 25285/NCTC 9343 has been synthesized using a linear glycosylation approach. One key step includes an α(1,4)-stereoselective [2 + 1] glycosylation of a 2,4,6-trideoxy-2-acetamido-4-amino-d-Gal p (AAT) donor with a poorly reactive axial C4-OH disaccharide acceptor. Mild acid-mediated deacetylation and a challenging [3 + 1] glycosylation are also highlighted. The strategy is inclusive of a single-pot, three-step deprotection affording PS A1 with alternating charges on adjacent monosaccharide units.